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Substantial Early Loss of Induced Pluripotent Stem Cells Following Transplantation in Myocardial Infarction

机译：心肌梗死移植后诱导多能干细胞的大量早期丢失

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The limited success of cardiac stem cell therapy has lately generated discussion regarding its effectiveness. We hypothesized that immediate cell loss after intramyocardial injection significantly obscures the regenerative potential of stem cell therapy. Therefore, our aim was to assess the distribution and quantity of induced pluripotent stem cells after intramyocardial delivery using in vivo bioluminescence analysis. In this context, we wanted to investigate if the injection of different cell concentrations would exert influence on cardiac cell retention. Murine-induced pluripotent stem cells were transfected for luciferase reporter gene expression and transplanted into infarcted myocardium in mice after left anterior descending coronary artery ligation. Cells were delivered constantly in aqueous media (15L) in different cell concentrations (group A, n=10, 5.0x10(5) cells; group B, n=10, 1.0x10(6) cells). Grafts were detected using bioluminescence imaging. Organ explants were imaged 10min after injection to quantify early cardiac retention and cell biodistribution. Bioluminescence imaging showed a massive early displacement from the injection site to the pulmonary circulation, leading to lung accumulation. Mean cell counts of explanted organs in group A were 7.51x10(4)+/- 4.09x10(3) (heart), 6.44x10(4)+/- 2.48x10(3) (left lung), and 8.06x10(5)+/- 3.61x10(3) (right lung). Respective cell counts in group B explants were 1.69x10(5)+/- 7.69x10(4) (heart), 2.11x10(5)+/- 4.58x10(3) (left lung), and 3.25x10(5)+/- 9.35x10(3) (right lung). Applying bioluminescence imaging, we could unveil and quantify massive early cardiac stem cell loss and pulmonary cell accumulation following intramyocardial injection. Increased injection concentrations led to much higher intracardiac cell counts; however, pulmonary biodistribution of transplanted cells still persisted. Therefore, we recommend applying tissue engineering techniques for cardiac stem cell transplantations in order to improve cardiac retention and limit biodistribution.
机译：心脏干细胞疗法的有限成功最近引起了关于其有效性的讨论。我们假设心肌内注射后立即的细胞丢失会严重掩盖干细胞疗法的再生潜力。因此，我们的目的是使用体内生物发光分析评估心肌内递送后诱导的多能干细胞的分布和数量。在这种情况下，我们想研究注射不同浓度的细胞是否会对心脏细胞的保留产生影响。小鼠诱导的多能干细胞被转染荧光素酶报告基因，并在冠状动脉左前降支结扎后移植到小鼠梗死的心肌中。将细胞以不同的细胞浓度不断地在水性介质（15L）中递送（A组，n = 10，5.0x10（5）个细胞; B组，n = 10，1.0x10（6）个细胞）。使用生物发光成像检测移植物。注射后10分钟对器官外植体成像，以量化早期心脏early留和细胞生物分布。生物发光成像显示从注射部位到肺循环的大量早期移位，导致肺积聚。 A组中移植器官的平均细胞计数为7.51x10（4）+/- 4.09x10（3）（心脏），6.44x10（4）+/- 2.48x10（3）（左肺）和8.06x10（5 ）+/- 3.61x10（3）（右肺）。 B组外植体的细胞计数分别为1.69x10（5）+/- 7.69x10（4）（心脏），2.11x10（5）+/- 4.58x10（3）（左肺）和3.25x10（5）+ / 9.35x10（3）（右肺）。应用生物发光成像，我们可以揭示和量化心肌内注射后大量早期心脏干细胞损失和肺细胞积累。注射浓度的增加导致心脏内细胞数量大大增加。然而，移植细胞的肺生物分布仍然持续。因此，我们建议将组织工程技术应用于心脏干细胞移植，以改善心脏保留能力并限制生物分布。

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